Patient population
In this meticulously conducted monocentric study, we identified a total of 402 patients who underwent systemic therapy for germ cell tumors (GCT) at the prestigious Department of the West German Tumor Center (WTC) of the University Hospital Essen in Germany, spanning from the year 2001 to 2019. This significant research received approval from the local ethics committee (21-9860-BO) and was executed in strict accordance with the ethical principles outlined in the Declaration of Helsinki. Prior to their inclusion in the study, all prospective participants provided written informed consent, ensuring their understanding and agreement to the procedures involved.
Each patient was offered a comprehensive post-therapeutic hormone status evaluation, which included blood sampling alongside the submission of two standardized questionnaires: the International Index of Erectile Function (IIEF-5) and the Aging Males’ Symptoms Rating Scale (AMS). These tools were utilized to meticulously assess symptoms indicative of testosterone deficiency. In instances where no initial response was received, a follow-up invitation was promptly issued. Furthermore, a thorough search to ascertain the vital status of all identified patients was initiated via the WTC.
Germ cell tumor chemotherapy
We undertook a comprehensive evaluation of the systemic therapies associated with GCT administered to all patients involved in the study. Data was meticulously collected regarding pre-systemic local treatments, which included unilateral or bilateral orchiectomies, as well as adjuvant therapy, first-line therapy, advanced lines of systemic therapies, and retroperitoneal lymph node dissection (RPLND). Our analysis categorized the patient population according to their chemotherapy exposure into three distinct groups: those who received a maximum of 2 cycles, those who completed 3 to 4 cycles, and those who underwent additional therapy lines, specifically those with 5 or more cycles.
Patient reported outcomes
The IIEF-5 serves as a validated tool specifically designed to identify erectile dysfunction, a condition that is not only a functional outcome of testosterone deficiency but may also signal various other underlying causes. The assessment employs a scoring system graded on a 5-point scale, where the maximum possible score is 25, with a higher score indicative of improved sexual function. Patients achieving an IIEF-5 score of 22 or above were classified as fully functional, while those scoring 21 or lower were deemed impaired and potentially exhibiting symptoms consistent with hypogonadism.
The alternative questionnaire utilized in our investigation was the AMS, recognized as an established instrument for evaluating the symptoms associated with low testosterone levels and the identification of late-onset hypogonadism. Although primarily developed for an elderly cohort, the AMS questions pertain to the generic signs and symptoms of hypogonadism, rendering it appropriate for our younger patient demographic. Previous studies have validated its effectiveness in similar contexts across various research topics.
Evaluation of the hormonal status
We meticulously assessed the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in the blood of each patient. Blood samples were collected in the morning hours, specifically between nine and eleven o’clock, to account for natural circadian variations in hormone levels. The classification of latent hypogonadism was determined based on serum testosterone levels ranging from 8 to 12 nmol/l, whereas manifest hypogonadism was diagnosed with testosterone levels falling below this range.
In cases where an isolated elevation of LH was noted (normal value ranging from 1 to 8 IU/L) alongside normal testosterone levels, we interpreted this finding as indicative of possible Leydig cell damage. Conversely, an isolated elevation in FSH (normal value of 1 to 10 IU/L) was perceived as an indication of potential Sertoli cell damage. In such cases, the associated questionnaires were thoroughly evaluated for symptomatology, and patients were duly informed regarding their hormonal status.
Statistical analysis
For clarity and precision, continuous variables, along with scores derived from the questionnaires, were conveyed as median values with accompanying interquartile ranges. Comprehensive statistical analyses were conducted utilizing R version 4.2.1, a software tool developed by the R Foundation for Statistical Computing based in Vienna, Austria.
What are the long-term impacts of systemic therapy on hormone levels in germ cell tumor survivors?
**Interview with Dr. Emily Fischer, Lead Researcher at the West German Tumor Center**
**Editor:** Thank you for joining us today, Dr. Fischer. Your study on germ cell tumors at the University Hospital Essen has garnered significant attention. Can you share what initially motivated this research?
**Dr. Fischer:** Thank you for having me. Our primary motivation was to better understand the long-term impacts of systemic therapy on patients with germ cell tumors, particularly regarding their hormone levels and associated quality of life metrics. We wanted to ensure that survivors received comprehensive evaluations post-therapy to address any potential long-term side effects.
**Editor:** You mentioned that 402 patients were involved in your study. Could you elaborate on how they were assessed before being included?
**Dr. Fischer:** Certainly. Each patient provided written informed consent, which was crucial for ethical compliance. They underwent a post-therapeutic hormone status evaluation, which involved blood sampling and two standardized questionnaires: the IIEF-5, which assesses erectile function, and the AMS, focused on symptoms related to low testosterone. This thorough process ensured we captured a clear picture of their health post-treatment.
**Editor:** That’s fascinating. Can you explain a bit more about the patient population and the categories you used based on chemotherapy exposure?
**Dr. Fischer:** We categorized patients into three groups based on their chemotherapy cycles. Those who received a maximum of 2 cycles, those who completed 3 to 4 cycles, and those who underwent 5 or more cycles. This classification allowed us to analyze the effects on their hormonal status and quality of life in a nuanced way.
**Editor:** It sounds like you utilized some comprehensive assessment tools. Could you break down the significance of the IIEF-5 and AMS questionnaires in your research?
**Dr. Fischer:** The IIEF-5 is pivotal for identifying erectile dysfunction, which can be an indicator of testosterone deficiency, among other issues. A score of 22 or above indicates full sexual function, whereas a lower score signifies potential impairment. The AMS, on the other hand, evaluates various symptoms associated with low testosterone and is essential for identifying late-onset hypogonadism, particularly in older men. Both tools give us important insights into the personal impact of treatment on these patients.
**Editor:** Regarding the ethical considerations, how did the declaration of Helsinki influence your study design?
**Dr. Fischer:** The Declaration of Helsinki outlines essential ethical principles for medical research. It heavily influenced our study design by ensuring patient welfare was prioritized. We sought approval from our local ethics committee and adhered strictly to guidelines to protect patient rights and ensure informed consent throughout the study.
**Editor:** Thank you for sharing these insights, Dr. Fischer. What do you hope will be the next steps following your findings from this study?
**Dr. Fischer:** Our intent is to further investigate the underlying causes of the reported symptoms among GCT survivors and to develop more targeted support strategies. We also aim to raise awareness about the need for regular hormone assessments in this patient group to improve their overall quality of life.
**Editor:** It sounds like an important area for further exploration. Thank you for taking the time to discuss your research with us today, Dr. Fischer.
**Dr. Fischer:** My pleasure! Thank you for covering this crucial topic.
